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Disorder Classification Defect (in

)

Ankyrin
Mutations in band 3 or
4.2 may also cause it
Unable to maintain
Hereditary Hereditary (AD) normal shape MCHC
Spherocytosis membrane defects increased

mutation in
Paroxysmal Nocturnal Acquired membrane phosphatidylinositol
Hemoglobinurea defect glycan A
Lack glucose-6-
phosphate
dehydrogenase
Cannot produce GSH to
protect cell from
oxidative stress Patient
suddenly turns yellow
Hereditary (XR) from Oxidative drugs -->
G6PD deficiency metabolic defect sudden anemia

Pyruvate Kinase Hereditary (AR)
Deficiency metabolic defect Impaired ATP synthesis

beta globin chain has
substitution at position 6
G6V mutation in b-chain
Homozygous = disease,
heterozygous = trait
Many other mutations:
Hemoglobin C is another
Hemoglobin S (Sickle Hereditary (AS) variant (milder in
Cell) qualitative Hb defect symptoms)

Hereditary quantitative
a - Thalassemia Hb defect β-thalassemia major:
Homozygous or
compound heterozygous
(β0/β0, β0/β+, or β+/β+)
β-thalassemia trait: β/β+
or β/β0
Mostly due to gene
deletions or
transcription/translation
Hereditary quantitative Hb decreased but Iron
β - Thalassemia Hb defect level increased

synthetic valves or
Mechanically induced microangiopathic
anemia disease

IgG anti-RBC that react
Warm AIHA Immune mediated optimally at 37°C

IgM anti-RBC that react
Cold AIHA Immune mediated optimally at 0 – 4°C

Cold Hemolysin IgG anti-RBC that react
Hemolytic Anemia Immune mediated optimally at cold temp,

Drug Induced Immune
Hemolytic Immune mediated

Alloimmune Hemolytic Immune mediated incompatible blood types Malaria Chronic Renal Failure Lead Poisoning Impaired production heme synthesis .

Iron deficiency Impaired production heme synthesis Anemia of Chronic Disease Impaired production heme synthesis B12 deficiency (other causes) Impaired production DNA synthesis Pernicious Anemia Impaired production DNA synthesis .

Folate Deficiency Impaired production DNA synthesis Reduced proliferation of stem cells or produce Aplastic anemia Impaired production neo-antigenic progeny Myelophthisic anemia Impaired production Bone Marrow Erythrocytosis Erythrocyte ++ EPO. or malignant (Polycythemia Vera) overproduction stem cells .

to oxidative stress protection from 2-3 day lagcomplement alternative period. sperical cells 2. But ultimately accumulation of Heinz bodies & membrane by Normocytic macros leads to “bite cells” Extravascular A. MCHC splenic cords d/dL) Increased 1. GPI anchor is NOT synthesized 2.Pathogenesis Severity Cell morphology &Labs 1.in American blacks Spherocytes may be sequestration (some function) present Heinz bodies (moderately damaged A0 in mediterranian RBC with precipitated cells).RBC's become rounded due to low surface area Normocytic to volume ratio. 55 (DAF). Extravascular Howell Jolly bodies hemolysis of inflexible (small dark nuclear spherocytes in the mild to moderate (6 – 9 remnant). variant (zero function) denatured globin 1. Initially pathway Intravascular Low platelet count lysis of severly damaged cells 3. Exposureno membrane. CD 59. then: 2. dehydration & change in morphology 3. low ATP 2. Extravascular echinocytes (RBCs w/ hemolysis thorny projections) . C8 binding proteins not available on cell 1. Shear stress slowly cause loss of membrane.

a-chains aggregate into tetramers making abnormal Hb. RBCs damaged by hemolysis anemia Target cells passing through fibrin cords or synthetic valves. HUS & DIC 2. Ineffective microcytosis Oxygen transport Hypochromia 2. Deoxygenated Hb's aggregate in cell. 3. 2. So hypoxia causes sickling. Extravascular (when HbF is (Ir)reversibly sickled hymolysis diminished) cells 1. membrance damage Major: severe Anisocytosis leads to Extravascular Trait: asymptomatic/mild Poikilocytosis 1. Results in Intravascular hemolysis Etiology is more & production of significant that the actual Schistiocytes: schistiocytes anemia fragmented RBCs .1. Microvascular damage & tissue ischemia as sickled cells Severe (3 – 8 g Hb/dL) aggregate & plug Symptoms develop Anisocytosis & vessles around age 6 months poikilocytosis. Also seen Microangiopathic (narrowed vessels) w/ TTP.

at extremities) 3. cryocyanosis of mild to moderate stable extremities anemia agglutination of RBCs 1. Abs attach to P Ag on RBC 3. complement mediated Intravascular hemolysis when RBC recirculates to warm area . macroglobulinemia. w/ infestions: hemolysis . 2.g. Extravascularphase Spherocytes formed due assoc. Abs bind to RBCs at macroglobulinemia 1. Abs bind to RBCs when blood is cooled (e.Autoab Can be sever & life to splenic macros EBV/mycoplasma. Or - infection and drug induced. body temp (Type II HSR) cause: acute 3. exposire to cold 2. cause: Idiopathic or secondary to autmimmune diseases.1. w/ CLL. diffuse large B cell lymphoma & splenic lymphoma. signals spleen to rid of threatening (4 – 6 g plucking Ab bound cell Chronic: RBC idiopathic or Hb/dL) membrane assoc. Primary cause idiopathic Lymphoma/leukemias or secondary cause other neoplasms. Waldenstrom 2.

Introduction of depends on prior immunogenic RBCs sensitization to Rh 2.1. impaired Hb synthesis Cells . and dose of blood Intravascular hemolysis exposed 1. IgM mediated factor. inhibits ala dehydrogenase and ferrochelatase microcytic Hypochromic 2.

to erythroid precursorsor 9 – 12 g Hb/dL Hypochromic Cells fish tapeworm 2. Chrons. DNA synthesis imparied. etc. presenece of a chronic illenss (infection. autoimmune disorder. 2. or malignancie). starts as normocytic – progresses to microcytic varies Hypochromia 1. Malabsorption hepcidin prevents due to terminal transfer ofileum iron diseases from Initially normocytic – (Celiac. pancytopenia neutrophils & eosionphils . mitochondria in macros progresses to microcytic Chronic pancreatitis. Megaloblastic precursors phagocytosed by macrocytic RBCs macros. Malabsorption pancytopenia due to neutrophils & achlorhydria and lack of eosionphils intrinsic factor 2. Cell differentiation halted 3. Megaloblastic precursors phagocytosed by macrocytic RBCs macros. DNA synthesis imparied. Hypersegmented 1. increases hepcidin 1. variety of cell sizes.). 4. Cell differentiation halted 3. Hypersegmented 4.

. Cell differentiation halted 3. erythropoietin receptor hyperfunction Secondary: ++ EPO. or antagonists (e. Hypersegmented 4. Malignancy or myelofibrosis crowds out bone marrow Dacrocytes.EPO. anemia may be dose 2. pancytopenia neutrophils & eosionphils 1. Primary: -. appropriate (hypoxia) or inappropriate (normoxia) 2. causes: Idiopathic. extramedullary leukocytes among hematopoesis mature cells 1. deficiency: decreased intake. marrow aplasia related. pancytopenia immature RBC's & 3.g. or idiosyncratic hypocellular bone 3. increased utilization. etc. 2. methotrexate) 2.1. pancytopenia (chloremphenicol marrow (mostly fat) 1. Megaloblastic precursors phagocytosed by macrocytic RBCs macros. chemical related. checmical related infections. DNA synthesis imparied.

lactic acidosis. protection from malaria infections .Labs Epidemiology Treatment Osmotic fragility test slenectomy Avoid oxidative stressors: Drugs: antimalarials. sulfa drugs More common in the Food: fava beans Mediterranian & African Others: prolonged areas since it offers hypoxia.

decent.Sickledex (cannot Hydroxyurea therapy distinguish between trait reduces frequency & and disease). Affects people of African severity of vaso- Electrophoresis. ++ in Italy & Greece. protection occlusive crises. survival DNA testing against malaria is now 50% upto age 50 Worldwide. More common in the US. Than a-thal regular blood elevated HbA2 &HbF (protection against transfusions required in Dx: electrophoresis malaria) severe form .

50 – 70% immune no compatible blood for Coomb's test hemolytic anemias transfusion 30% immune hemolytic anemias Increased frequency w/ older adults .

Blood type mismatch more common than catching blood borne diseases from Coomb's test transfusion cease transfusion ++ serum iron ++ serum ferretin --TIBC ++ serum ferretin .

-.serum ferretin ++ TIBC worldwide: worse in ++ RDW developing countries iron supplements -.serum cobalamine ++ methylmalonic acid ++ serum homocysteineserum Abs to intrinsic factor or gastric parietal cells Shillings test vitamin supplement .serum cobalamine ++ methylmalonic acid more common in vegans ++ serum homocysteine & breast fed infants of vegans Shilling's test & alcoholics? vitamin supplement -.serum iron -.serum iron ++ serum ferretin most common anemia in -.TIBC hospitalized patients -.

more common in 50 – 200 micro gram ++ serum homocysteine alcoholics daily vitamin supplement after ACD. most common cause in individuals age ≥ 60 associated with cigarette smoking (appropriate phlebotomy for ≥54 secondary form) hematocrit .

3 BPG shifts O2 binding curve to the right .Complications/Other symptoms splenomegaly Jaundice Cholelithiasis (pigment stones or bilirubinate) Aplastic crisis w/ parvovirs infections Rare hepatic/cerebral vein thrombosis due to platelet dysfunction increasees risk of AML acute hemolysis may lead to death ++ 2.

bone pain) Autosplenectomy (leads to infections w/ S. pneumonae & H.Sickle crisis (e. influenzae) Hemolysis causes hyperbilirubinemia & pigment stones iron overload from blood transfusions Bone expansion due to increased hematopoesis? .g.

precipitated by cold hemoglobinunria frequent .

burning sensation.Back pain. anaphylaxis .

sensory ataxia. sensory Achlorhydria ataxia. & paresthesia atrophic gastritis (beefy tongue) Neurological deficits – spinal cord dorsal & lateral columns: (Subacute combined degenration) w/ spastic paraperisis.neurological deficits: spinal cord dorsal & lateral columns Gastric (Subacute atrophy combined (++ risk of gastric degenration) w/ spastic carcinoma) paraperisis. & paresthesia Cortical: dementia .

this supplement Tx might improve anemia but worsen neurologic problems ++ blood viscosity ++ cardiovascular complications ++ thrombosis & hemorrhage .If patient is deficient in cobalamine.

acute/chronic blood loss.-/a- severe anemia Hydrops fetalis: -/-.due to splice mutation or promoter region mutation .then microcytic Iron Deficiency hypochromic malnutrition increased utilization (e.a/aasymptomatic or malaria) βthal minor HbH disease: -/-.Disorder Classification Cause 1st normocytic normochromic. a/a- asymptomatic Mediterranian. or hemodialysis Ferrochetalase lacks substrate to complete heme synthesis reduced αglobin synthesis in any of 4 α Thalassemia Microcytic Anemia total genes gene deletion is most common cause Silent carrier: -/a.g. Africa & Southest Asia αThalassemia trait: (protection against -/-.-/- lethal in utero inherited defect in 2 β Thalassemia Microcytic Anemia genes which destroys normal RNA splice junction- causing no globin synthesis beta globulin is produced. during pregnancy).

children ingest in old
houses because they
Lead Poisoning microcytic anemia used lead paint
genetic, aquired
(myelodysplastic
syndromes), Reversible
(alcohol, lead, vitamin
B6 deficiency, copper
Sideroblastic Anemia microcytic anemia deficiency, isoniazid)

Pathogenesis

1st stage: iron requirement exceeds intake-
progressive depletion of bone marrow iron
stores-

then stores decrease so dietary absorption
increases (hepcidin decreases and stops
interfering) then deficiency impairs iron
synthesis- causing normocytic anemia,
hypochromic microcytic and can cause
dysfunction of ironn containing cellular
enzymes

β chains aggregate into tetramers-Hb H
disease- high affinity for O2 so cause tissue
hypoxia

oxidation and precipitation of intracellular
protein aggregates promote RBC sequestration
by macrophages
HbBart- γchain tetramers bind o2 with
avidity

impaired or no creation of β chains

alpha chains do not form tetramers so they
precipitate within the cell

lead inactivates ALA dehydrase and
ferrochetalase in heme synthesis and produces
microcytic sideroblastic anemia with ringed
sideroblasts in bone marrow, also lead inhibits
rRNA degredation- causing RBCs to retain
aggregates of rRNA (basophilic stippling)

defect in heme synthesis- x linked defect in δala
synthase gene

glossitis. death by age 20 . serum LDH. concave nails serum iron. dizziness. SOB. cheilosis. weakness.shows anemia fatigue.just mild microcytic anemia bilirubin Intermedia.β0/β0 microcytic hypochromic anemia. splenomegaly.generally d/t β+/β+ οr β0/β+ may need transfusions but not severe Major/Cooley Anemia.absent iron stores Evaluation for severe anemia in HBH hemolytic anemia splenomegaly d/t increased RBC turnover Peripheral smear Electrophoresis DNA testing for prenatal diagnosis CBC.Signs and Symptoms Diagnosis CBC.Plummer-Vinson syndrome high serum ferritin= iron body stores.low levels <12ng/mL bone marrow. pallor Hgb Pica. indirect Minor.low. bone deformities. smear. serum haptoglobin. serum (koilonychia) severe caused by postcricoid iron binding capacity- esophageal web.

aggregates of rRNA in Abdominal colic. but more needs to be produced of those than a normal HbA1 because they have a higher O2 affinity and don't unload it very well splenomegaly d/t increased RBC turnover lead lines and erythrocyte basophilic lead lines on gingivae (burton lines) and on stippling (retained metaphyses of long bones on xray. Anemia.hyperplasia of bone marrow and extramedullary hematopoiesis in liver and spleen produced. encephalopathy RBCs) .

transferrin increased. target cells. Hb serum iorn normal. late.microcytosis and hypochromia Stage 5.iron deficiency affects tissues anisocytosis. transferrin sautration decreases. serum ferritin falls.microcytic serum ferritin receptor hypochromic level rises normal appearing RBCs and indices develops Stage 4. serum iron decreased.normocytic absorption causes anemia increase Transferrin oral iron impaired. punctuate and RBC elevated but cells diffuse basophilia microcytic . poikilocytosis.Cell morphology Labs Treatment bone marrow iron stores. target blood transfusions in cells severe anemia Hb<6 severe erythroblasts. small pale RBCs. increase iron early.

pyridoxine .ringed sideroblasts with iron laden mitochondria in bone increased iron and marrow ferritin. normal TIBC B6.

Complications/Other symptoms iron overload from transfusions bone expansion due to increased hematopoiesis extramedullary hematopoiesis iron overload due to anemia and hypoxia down regulation of hepcidin .

Abdominal colic and sideroblastic Anemia. Succimer used for chelation for kids (It “sucks” to be a kid who eats lead). Dimercaprol and EDTA are 1st line of treatment. Encephalopathy and Erythrocyte basophilic stippling. Drops—wrist and foot drop. .LEAD: LEAD: Lead Lines on gingivae (Burton lines) and on metaphyses of long bones D on x- ray.

Orotic Aciduria .Disorder Classification Cause MEGALOBLASTIC Vitamin B12 Deficiency Folate Deficiency NON-MEGALOBLASTIC Liver Disease Alcoholism Reticulocytosis Metabolic Disorder.

metabolizing methylmaloyl CoA.Pathogenesis Signs and Symptoms Diagnosis B12 needed for tetrahydrofolate. converting homocystein to methionine.no B12 gives same symptoms as no folate but also demyelination is what leads to CNS effects .

Cell morphology Labs Treatment .

Complications/Other symptoms .

Disorder Classification NONHEMOLYTIC ANEMIA normocytic normochromic or Anemia of Chronic Disease microcytic hypochromic Aplastic Anemia normocytic normochromic Kidney Disease normocytic normochromic Myelophthtisic Anemia HEMOLYTIC ANEMIA INTRINSIC EXTRAVASCULAR Hereditary Spherocytosis Pyruvate Kinase Deficiency Sickle Cell Anemia HbC Defect INTRAVASCULAR G6PD Deficiency Paroxysmal Nocturnal destruction of RBCs by Hemoglobinuria complement system .

PCH/ Donath-Landsteiner presence of hemoglobin in Syndrome urine after exposure to cold Microangiopathic Anemia mechanical destruction Macroangiopathic Anemia mechanical destrucion in Infectious anemia .EXTRINSIC antibodies directed against blood causes them to burst- either warm or cold(cold Autoimmune Hemolytic aglutinin and paroxysmal Anemia cold) IgG (or A) bind to RBCs at Warm Agglutinin warm temperatures autoimmune disease high concentration of IgM directed Cold Agglutinin at blood cells Paroxysmal Cold Hemoglobinuria.

and maligancy o Toxic exposures • Irradiation • Drugs or chemicals- • marrow suppression can be dose related predictable and reversible (benzene.d/t primary defect in stem cells o suppression of altered stem cells by T-cell immune mechanisms insufficient erythropoietin autosomal dominant and recessive inheritance due to mutation in PKLR gene. streptomycin) o viral infections.fanconi anemia. telomerase defects o idiopathic.b.hepatitis (non-a. sulfonamides.less glycolysis means reduction in ATP in red blood cells x-linked recessive deficiency. fava beans defect in PIGA enzyme required to make GPI. immune activation. located on X chromosome .c or g) o inherited diseases.mediterranean and african (mediterranean is worse) antimalarials.Cause chronic infection. antimetabolites) • idiosyncratic (chloramphenicol. chlorpromazine. alkylationg agens.

idiopathic primary. secondary d/t lymphoproliferative disease in adults or an infection in children (M.molecular mimicry DIC. HIV) following an infection. Thrombotic Thrombocytic Purpura. pneumo. Lupus.when microorganism triggers antibodies formation that cross react. Hemolytic Uremic Syndrome. mono. Malignant hypertension .

and CD59 which blocks c9 from binding hemoglobin and on cell. difficulty intravascular hemolysis swallowing.NAKATPase pump halts so potassium leaks • Splenomegaly out cell shrinks and diesand is eaten by spleen • Leg ulcers without the GPI yu have no CD55 that prevents c3.red dicoloration of urine d/t convertase.some have that RBCs cannot protect themselves against so abdominal pain.instead it is sequestered and not exported by duodenal epithelim and macrophages • also inflammatory cytokines increase production of WBCs which come from the same progenitor as RBCs so decreased erythropoiesis anemia stupid o Hypocellular marrow- hematopoietic cells replaced by fat o Infections- granulocytopenia o Bleeding- thrombocytopenia o Anemia • Anemia • Cholecystolithiasis because RBCs cannot synthesize ATP cellular death • Jaundice occurs. ED.at night decreased respiratory rate causes hemosiderin.Pathogenesis Signs and Symptoms • elevation of interleukin-6 stimulates hepcidin release from liver which reduces ferroportin so iron is not released. blood clots . anemia acidification of blood and activation of complement symptoms.

heart valves . hyperbilirubinemia at low body temp. macrophages in spleen pick off pieces of membrane turning them into spherocytes.IgG or A bind to polysaccharides on RBC in warm temps. IgM binds to polysaccharide.intravascular hemolysis mechanical destruction in small vessels- endothelial layer of small vessels are damaged- fibrin deposition and platlet aggregation so the blood going thru this gets fragmented and results in intravascular hemolysis mechanic destruction in large vessels. when they return to warmth. increased flexible so they will lyse MCV. complement is triggered so RBCs lyse polyclonal IgG anti-P autoantibody binds to RBCs in cold so red cells are lysed when blood returns to warmer central circulation.not as severe anemia.

high • TIBC low • Transferrin receptor- normal bone marrow.low • Serum ferritin. Bilirubin . Reticulocyte counts.Diagnosis Cell morphology Labs • Underlying disorder • CBC-anemia • Serum iron.replaced by fat and CBC for pancytopenia no cells CBC.

helmet cells .positive indirect coombs test (direct coombs test looks for antibodies attached to surface of RBCs) schistocytes. helmet cells schistocytes.

Complications/Other Treatment symptoms epo & iron treatments + underlying disorder • Equine antithymocyte globulin. cyclosporine • Hematopoietic cell transplantation • Cytokines • Surgery in thymoma associated RBC aplasia not generally necessary- splenectomy and blood transfusion if severe . corticosteroids.

Name Poiklocytes Spherocyte micro-spherocyte irregularly contracted cell Elliptocyte Ovalocyte Dacrocyte .

Target Cell Stomatocyte Keratocyte Schistocyte Echinocyte (crenated cell) Acanthocyte Sickle Cell Boat-shaped Cell .

S-C poikilocyte Rouleaux Basophilic stippling Cabot pappenheimer bodies howell-Jolley Bite Cell Ringed Sideroblasts .

Teardrop cell .

Image/ Description

spurr cell

basophilic remnants found in RBC- normally removed by spleen

autoimmune hemolysis hereditary elliptocytosis megaloblastic anemia (also hypersegmented PMNs) marrow failure .Disorders Seen hereditary spherocytosis.

Liver disease. Thalassemia helmet cell. traumatic hemolysis abetalipoproteinemia and liver disease sickle cell anemia . Asplenia.DIC. TTP/HUS.HALT said hunter to his target: HbC disease.

alcohol abuse. lead poisoning.Anemia of Chronic Disease. Excess iron in mitochondria = pathologic . Thalassemias seen in patients with functional hyposplenia or asplenia G6pD deficiency sideroblastic anemia.

Bone marrow infiltration.myelofibrosis. thalassemia .

hemoglobin. microcytic and normocytic Mean Corpuscular Volume (MCV) anemia Mean Corpuscular measure of average amount of hemoglobin w/in an RBC- Hemoglobin(MCH) indicates hypochromia Mean Corpuscular Hemoglobin measure of average percentage of hemoglobin in a single Concnetration (MCHC) RBC.Test Explanation Anti-parietal cell antibody Blood smear See-Cell morphology Bone marrow biopsy includes all of the following: Red blood cell count. eosinophils. MCV. RBC indices.hemoglobin over hematocrit percentage . MCH. Neutrophils. monocytes. mean platelet volume (MPV) RBC count Hemoglobin (Hgb) total amount of hemoglobin in blood percentage of blood volume that is made up by RBCs- Hematocrit (Hct) measured by height in column after centrifugation RBC indices differentiating macrocytic. lymphocytes. hematocrit. MCHC. basophils. WBC and differential. RDW. blood smear. platelet Complete blood count (CBC) count.

ferritin is also an acute phase reactant protein (rises 1-2 days after onset of acute illness and peaks 3-5 days after) most sensitive test for iron Ferritin deficiency anemia .3 diphosphoglycerate Erythropoietin indicator of available iron stores.Red Cell Distribution Width (RDW) indication of anisocytosis.1ng/ml of serum ferritin is equal to 8mg of stored iron.variation in RBC size indication of ability of bone marrow to respond to anemia- Reticulocyte Count so if production is adequate WBC Neutrophils Lymphocytes Monocytes Eosinophils Basophils Platelet Count Mean Platelet Volume (MPV) evaluation of thrombocytopenia 2.

nonspecific for indicating type of hemolytic anemia.haptoglobins bind to hemoglobin in blood so complex can be metabolized so Serum haptoglobin more hemolysis causes diminished haptoglobin blood Urinary Hemosiderin Positive Acid Hemolysis (HAM) Serum Bilirubin total bilirubin-direct+indirect .Folic acid Heinz body Hemoglobin electrophoresis Intrinsic factor Iron Testing blood test iron level (Fe) Total Iron Binding Capacity Transferrin Transferrin Saturation differentiate iron deficiency anemia from anemia of chronic disease or other low iron anemias.it is a receptor on cells Transferrin Receptor Assay with high requirement for iron Sickle Cell Screen TSH Total blood volume Vitamin B12 Zinc protoporphyrin Direct Coombs Test Indirect Coombs Test Donath Landsteiner Test identify presence of intravascular hemolysis.

Indirect Bilirubin Direct Bilirubin Newborn bilirubin Urine bilirubin Erythrocyte Fragility .

7-6.Normal Results M-4. F 37-47%.2-5.4 m14-18g/dL F:12-16g/dL M42-52%. F4.1. pregnant >33% 80-100fL 27-33pg 33-37% .

5-1.5% 0.0% 25-100 150.5% or 2% (higher in infants) 5000-10.000 .000-400.000-4.000 55-70%. 100-700 1-4%.11.5-14. 50-500 0.5-1.4fL 12-300ng/ml M. 10-150ng/mL F .000 7. 2500-8000 20-40% 1.4-10.

m80-180mcg/dL.5-2. f 60-160mcg/dL 250-460mcg/dL 215-365mg/dL 20-50%m.2g/L 0.3-1mg/dL .4mg/L 50-220 mg/dL or 0. 15-50%f M2-5mg/L.9-4. W1.

3mg/dL 1.0.2-0.0-12mg/dL 0-0.02mg/dL .8mg/dL 0.1-0.

in response to decreased O2 carrying capacity of abnormal hemoglobin.Increased • Erythrocytosis • Congenital heart disease • COPD • Polycythemia vera • Severe dehydration • Hemoglobinopathies • Thalassemia trait.d/t free hemoglobin in blood so automated counter sees hemoglobin and incorporates that into calculations • Cold agglutinins.more RBCs produced same as RBC Same as RBC • Pernicious Anemia • Folic Acid deficiency • Antimetabolite therapy (methotrexate.false calculation .B12 and folate inhibitors) • Alcoholism (malnutrition) • Chronic Liver Disease macrocytic anemias • Spherocytosis: it’s an automated false perception because of they variation in shape • Intravascular hemolysis.

chronic hepatitis .due to release of premature RBCs into blood stream (they are larger) • Hemolytic anemia.marrow attempts to compensate for shortened RBC survival time by producing large amounts of RBCs so reticulocytes are released into blood • Hemorrhage. cirrhosis. or folate deficiency • valvular heart disease • immune thrombocytopenia • massive hemorrhage(release of immature platelets are larger and increase MPV) • vitamin b12 or folate deficiency (megaloblastic changes affect megakaryocyte line so larger platelets are produced that may have nuclei so MPV increased) • Myelogenous leukemia (abnormal platelets formed by neoplastic megakaryocytes) • Hemochromatosis • Hemosiderosis (increased iron stores in tissues stimulate ferritin production for storage) • Megaloblastic anemia • Hemolytic anemia (iron is released in bloodstream so ferritin is stimulated to store excess fee iron) • Alcoholic/inflammatory hepatocellular disease • Inflammatory disease • Advanced cancers (ferritin is an acute-phase reactant protein increased with acute diseases) • Chronic illnesses.3-4 days later • Hemolytic disease of newborn • Treatment for iron. b12.leukemias.• Iron deficiency anemia • B12 or folate deficiency: RBC fragmentation alter size and shape but also those that were produced before deficiencies are there • Hemoglobinopathies • Hemolytic anemias • Posthemorrhagic anemias.

iron deficiency anemia increased in iron deficiency Paroxysmal Cold Hemaglutinin • biliary obstruction.because after attaching to hemoglobin haptoglobin is excreted by liver in bile • infection • collagen rheumatic diseases • nephritis • ulcerative collitis.d/t it being an acute phase reactant protein paroxysmal nocturnal hemoglobinuris .

sickle cell anemia. Crigler. hemolytic anemia. sepsis. obstructions . hepatitis. transfusion reaction. Gilbert Syndrome (interruptions in bilirubin conjugation) gallstones. hemolytic jaundice. Najjar. Neonatal hyperbilirubinemia. cirrhosis. extrahepatic duct obstruction (if you can't excrete bilirubin blood levels rise) liver metastasis (intrapeatic or hepatic duct obstruction) Cholestasis(bile cannot be excreted) gallstones.Erythroblastosis fetalis. pernicious anemia.

d/t overhydration • Rheumatoid/collagen vascular diseases • Lymphoma • Multiple myeloma • Leukemia • Hodgkin disease • Iron deficiency anemia • Thalassemia α and β • Anemia of chronic illness microcytic anemias.Decreased • Anemia • Hemoglobinopathy/ blood dyscrasias • Cirrhosis • Hemolytic anemia.d/t decreased survivial • Hemorrhage • Dietary deficiency • Bonemarrow failure • Prosthetic valves • Renal disease • Pregnancy. hypochromic anemia • Iron deficiency anemia • Thalassemia .

not clinically applicable • Pernicious anemia and folic acid deficiency • Iron deficiency anemia • Aplastic anemia • Radiation therapy • Marrow failure • Adrenocortical hypofunction • Anterior pituitary hypofunction • Chronic diseases • Aplastic Anemia • Chemotherapy-induced Myelosuppression: inadequate bone marrow production releases small platelets • Wiskott-Aldrich syndrome telets) Wiskott-Aldrich syndrome • Iron deficiency anemia: less iron stores so less ferritin is required • Severe protein deficiency .

free hemoglobin after lysis is bound to haptoglobin and used up but liver can't replace fast enough before levels drop • transfusion reactions • prosthetic heart valves-d/t RBC mechanical trauma/lysis • primary liver disease • hematoma • tissue hemorrhage we don't care about decreased.it just means things are doing fine .• hemolytic anemias.

.

Extra Information MCHC= hemoglobin/hematocrit x100 .

if it is below. even with an elevated reticulocyte level .reticulocyte index should be 1.it is the reticulocyte count x (patient's hematocrit/ normal hematocrit) a good marrow response should be 1.

is =serum iron level/total iron binding capacity x 100 .

.

Disorder Classification Related to Vessels and/or Primary Platelets Vessel Wall Abnormalities Scurvy Ehler's Danlos vessel disorder Cushing's Syndrome Aging Senile purpura Henoch-Schonlein Purpura leukocytoclastic angiitis Hereditary Hemorrhagic Telangiectasia (Osler-Weber- Rendu Syndrome) Waldenstrom's lymphoplasmacytic Macroglobulinemia lymphoma Amyloidosis Drug Reactions Infections Platelet Disorders .

quantitative platelet Thrombocytopenia dysfunction Immunologic Idiopathic ThrombocytopeniaPurpura platelet destruction Drug-Induced platelet destruction Thrombotic microangiopathies Thrombotic platelet overactivation and thrombocytopenic Purpura use platelet overactivation and Hemolytic Uremic Syndrome use Platelet function abnormalities .

Von Willebrand's Disease defect of platlet adhesion Bernard-Soulier Disease defect of platelet adhesion Aspirin defect of platlet aggregation Glanzmann's Thrombasthenia defect of platelet aggregation Secondary related to Clotting Factors Hen Hemophilia A deficiency of clotting factors Hemophila B deficiency of clotting factors Vitamin K Deficiency deficiency of clotting factors related to platelets and Combined clotting factors Von Willebrand's Disease .

DIC Liver Disease Dilutional .

rixkettsiosis ricketssial and meningococcal diseases . history of autoimmune disease with autoantibodies.Cause vitamin C deficiency age related atrophy of vascular supportive tissues autosomal dominant somatic mutation in MYD88. somatic mutation in CXCR4. HIV. liver inflammation.

myelophthisis.chronic idiopathic disorder • Alcohol • Quinidine • Heparin • Sulfa • Cytotoxic drugs • Thiazide diuretics • Deficiency of vWF metalloprotease (ADAMTS13)- accumulation of high molecular weight multimers of vWF promote platelet microaggregate formation post exposure to Shiga toxin or vero toxin by E. Bernard Soulier. Glanzmann's . Acute leukemia. exposure to drugs/chemicals.acute reaction to viral infection • In adults. DIC • Dilution of platelets: multiple transfusions • Secondary to AIDs and SLE • In children.• Decreased production: irradiation. Aspirin.coli 0157:H7 or Shigella dysenteriae vWillebrand's Disease. aplastic anemia • Unreplaced loss of platelets: splenic sequestration.

most common heritable bleeding disorder autosomal recessive deficency of platelet GPIb autosomal recessive deficiency of platelet GPIIb-IIIa x linked genetic disorder Factor 8 deficiency x linked genetic disorder Factor 9 deficiency • Fat malabsorption from pancreatic or small-bowel disease • In neonates d/t deficient exogenous vitamin K in breastmilk and incomplete intestinal colonization .genetic.

prostate. amniotic fluid emboli. hemolytic transfusion reactions multiple transfusion of stored blood .gnegative sepsis • Trauma • Immunologic mechanisms. pancreas.immune complex disease. abruption placentae • Cancer (most commonly lung.• Release of tissue thromboplastin • Activation of intrinsic pathway of coagulation • Secondary activation of fibrinolytic system • Most commonly in obstetric complications- toxemia. stomach) • Infection. retained dead fetus.

blurring. weight loss. and renal involvment malformation of venules and capillaries of mucous and skin weakness. chronic oozing of blood from nose and gums. capillaries and venules. peripheral neuropathy. fatigue. vascular damage lymphadenopathy. dermal poor vascular support hyperelasticity. gastrointestinal arterioles. tissue fragility hemorrhagic areas on back of hands and forearms hemorrhagic urticaria (palpable purpura) fever. small vessel vasculitis where IgA and C3 are deposited on arthralgias. headache vessel damage immune complex deposition with hypersensitivity vasculitis involve vascular endothelium leading to necrosis and rupture of small blood vessels . from sluding of hyperviscous blood because of all of the IgM loss of vision. articular hypermobility. cancer of B cels creating a bunch of igM.gingival hemorrhages • bleeding into muscles and subQ tissue • hemorrhagic perifolicular hyperkeratotic papules- surrounded with twisted lack of collagen cross-links corkscrew hair vascular bleeding.Pathogenesis Signs and Symptoms • extensive primary hemostatic bleeding.

and also the risk of maternal thrombosis antibodies activating platelet is increased aggregation • Thrombocytopenia. bloody • Platelet constant activation leads to thrombocytopenia diarrhea either defect in platelet adhesion or in platelet aggregation Mucocutaneous bleeding . • Platelet derived hyaline microaggregates (microvascular • Anemia platelet thrombi) block and cause damage to RBCs as they • neurologic deficit pass.due to thrombocytopenia.intravascular abdominal pain. • Petechial Cutaneous Bleeding • Intracranial bleeding • Oozing from mucosal decreased platelets lead to decreased clot formation and surfaces • Antiplatelet antibodies coat and damage platelets • Platelets removed selectively by splenic macrophages • Platelets not removed by spleen can become activated due • Petechia to antibody attachement and cause aggregation and • Purpura thrombosis • Mucosal bleeding • In pregnant women IgG antibodies can cause fetal • Thrombosis. pass.intravascular • renal dysfunction • Platelet constant activation leads to thrombocytopenia • fever • Thrombocytopenia • Anemia • Renal insufficiency and • Platelet derived hyaline microaggregates (microvascular failure platelet thrombi) block and cause damage to RBCs as they • Prodrome vomiting.thus hemolytic anemia.thus hemolytic anemia.

intracranial coagulation cascade cannot occur bleeding) . IX. easy bruising.when severe factor VIII deficiency NO petechiae and purpura perioperative/postop bleeding. so there is bleeding bleeding time irreversibly acetylates cyclo-oxygenase. proteins c &s) to γglutamyl • Easy bruisability carboxylase residues which allows calcium to bind to the 2 • Mucosal bleeding negatives and then for the factors to bind to negative surfaces • Hemorrhagic disease of on platelet lipid membrane. GI. preventing platelet production of thromboxane A2 • Bleeding into tissues • Hemarthroses • Muscle hematomas • Retroperitoneal hemorrhage lack of factor 8 cofactor on intrinsic pathway leads to • Excessive bleeding after bleading from inabiity to activate factor X surgery • Bleeding into tissues • Hemarthroses • Muscle hematomas • Retroperitoneal hemorrhage lack of cofactor 9 leads to inabiility to activate factor 10 with • Excessive bleeding after factor 8 surgery Vitamin K is required as a reucing agent to reduce glutamyl • Bleeding residues on factors (II.clinically mild. Without vitamin K in its reduced newborn (cutaneous.• Type 1(dominant).they are • Easy bruising normal in number but unable to for active high-molecular • Mucosal bleeding weight nultimers. reduced levels of vWF • Mild to moderate • Type 2 (dominant) –qualitative defects in vWF. VII.marked deficiency of vWF and severe • Increased menstrual phenotype bleeding vWF is the adhesion molecule of endothelium that GPIb-IXV • Abnormal bleeding after on platelets binds to so that the shear rates don't pull off the surgical procedures platelet. form you have no electron donor to form those factors so intrathoracic. heavy menstural bleeding. X.mild to moderate bleeding • Prolonged bleeding time • Type 3 (recessive). epistaxis. without gp1B there is no initial adhesion of platelets on abnormally prolonged vascular endothelium. bleeding gums.

particularly 2.widespread clotting with consummption of platelets and thrombotic phenomena and coagulation factors. 5. 8. and fibrinogen hemorrhage coagulopathy because all factors except vWF produced in liver persistent bleeding from surgical wounds .

hematuria at age less than 20 .distinguish HSP from hypersensitivity vasculittis: palpable purpura. abdominal angina. digestive tract hemorrhage.Diagnosis Labs raised IgA levels and raised CRP.

LFT. increased when caused by increased platlet destruction • CBC with platelets • Normal or increased megakaryocytes • Exclusion of other thrombocytopenic disorders (drugs. • Decreased platelet count • Prolonged bleeding time • Bone marrow aspiration shows megakaryocytes decreased when platelet production problem. alcohol. viral infections) • Decreased platelet count • Coagulation studies. aPTT. platelet count . • PTT reduce haptoglobin) • Fibrinogen • Bleeding time prolonged Serum bilirubin • PT. bleeding time. aPTT. lymphoproliferative disorders. elevated LDH elevated reticulocytes. thrombin time/fibrinogen normal PT. thrombin time/fibrinogen normal Serum bilirubin • Blood smear: schistocytes and helmet cells • Cbc with platelets • Increased megakaryocytes • Peripheral blood smear • Decreased platelet • Coombs test • Negative direct coombs test • LDH • Evidence of intravascular hemolysis (elevate • PT bilirubin. hep C and HIV • Normal PT and aPTT and Thrombin tests time/fibrinogen • Megakaryocytes are increased • Prolonged bleeding time • Decreased platelet count • Normal PT and aPTT and Thrombin time/fibrinogen • Megakaryocytes are increased • Blood smear: schistocytes and helmet cells • Cbc with platelets • Increased megakaryocytes • Peripheral blood smear • Decreased platelet • Coombs test • Negative direct coombs test • LDH • Evidence of intravascular hemolysis (elevate • PT bilirubin. PTT. autoimmune • Prolonged bleeding time diseases. elevated LDH) • PTT • Bleeding time prolonged • Fibrinogen • PT.

bleeding time. platelet count normal but bleeding time is prolonged PT. PTT. • Impaired adhesion prolongs bleeding time • Deficiency of factor VIII. • Normal platelet count. Thrombin Time and plasma factor VIII level Fibrinogen assay PT. bleeding time. prolonged aPTT vWF assay: total plasma vWF. PT. PTT. platelet count all are normal but bleeding time is prolonged PT. vWF function. bleeding time. platelet count normal but bleeding time is prolonges • Platelet count • Bleeding time normal • PT • Platelet count normal • PTT • PT normal • Factor VIII and X assays • aPTT prolonged • vWF activity and antigen and multimer • thrombin time/ fibrinogen assay normal composition • Factor VIII assay • Platelet count • Bleeding time normal • PT • Platelet count normal • PTT • PT normal • Factor VIII and X assays • aPTT prolonged • vWF activity and antigen and multimer • thrombin time/ fibrinogen assay normal composition • Factor IX assay prolonged PT and aPTT . PTT.

thrombin time. PT. and thrombin time PT. prolonged bleeding time. prolonged PT or aPTT . aPTT. bleeding are prolonged thrombocytopenia. thrombocytopenia. aPTT. increased fibrin and fibrinogen degredation products.microangiopathic hemolytic anemia with fragmented red cells (schistocytes).

Treatment Complications/Other closele related to and may be a systemic form of IgA neuropathy.most common cause of glomerulonephritis .

abdominal pain. corticosteroids and plasma diarrhea. arrhythmias by exchange myocardial damage hemodialysis and supportive care . confusion or coma. n/v.• Oral corticosteroids • IV immune globulin • IV anti-D immune globulin • Splenectomy • Thrombopoietin receptor agonist drugs- • Rituximab • Other immunosuppressants • Weakness.

vasopressin analog stimulates release of vWF into plasma and increases levels of factor VII • vWF replacement those treated in early 80s got HIV from plasma elements • Normal hemostasis >30% of normal factor 8 and 9 levels • Most patients have <5% levels • Bleeding severity depends on bleeding levels warfarin inhibits vitamin K epoxide reductase. the reaction that restores electrons to vitamin K so it can be a donor again.• desmospressin.for warfarin overdose give fresh vitamin K frozen plasma and vitamin K .

also give vitamin K .fix the liver.

Protein S Prothrombin Time (PT) Thromboelastography Thrombosis indicators .Test Activated Clotting Time Antithrombin III Bilirubin Coagulating factor Concentration CBC D-Dimer DIC scfeening Fibrinogen Partial Thromboplastin Time (PTT) Plasminogen Plasminogen activator inhibitor-1 (PAI-1) antigen Platelet aggregation Platelet antibody Platelelt Count Platelet function Assay Protein C.

Explanation Normal Results .

Increased Decreased Extra Information .

amyloid purpura Normal normal Glanzmann's thrombasthenia prolonged normal Bernard Soulier Syndrome prolonged normal or decreased Factor XII deficeincy Normal normal C1NH Deficiency Normal normal Anemia Diagnostic Flow Charts .Laboratory Screenign Tests in Selected Hemorrhagic Disorders Disorder Bleeding Time Platelet Count Vascular Bleeding usually prolonged normal Thrombocytopenia prolonged decreased Qualitative platelet defects prolonged normal Hemophilia A Normal normal Hemophilia B Normal normal von Willebrand Disease prolonged normal DIC prolonged decreased Vitamin K deficiency/ Warfarin Normal normal Aspirin prolonged normal Liver failure. early Normal normal liver failure end stage prolonged decreased uremia prolonged normal congenital afibrinogenemia prolonged normal factor V deficiency Normal normal factor X deficiency.

binucleate or bilobed with 2 halvs as mirror images. extranodal is rare. more common inmen except for peak incidence for certain nodular sclerosing type subtypes 20-40 years old 50% cases associated with may be associated with HIV EBV and immunosuppressions Constitutional ("B") signs/symptoms. CD15+ and Reed Sternberg cell CD30+ Bcell origin Hepatitis B HBsAg HBeAg Acute + + Chronic + + Resolved . except those of lymphoblastic Sternberg cells T cell origin Binodal distribution. single group of nodes. peripheral nodes. noncontiguous Lymphoma spread majority involve B cells- characterized by Reed. prognosis) Prognosis is much extranodal involvment better than with non-Hodgkin common.low grade fever. weight fever constitutional loss signs/symptoms tumor giant cell.young adulthood and >55. - . - Vaccinated .Hodgkin vs Non Hodkin Lymphoma Hodgkin Non-Hodgkin localized. contiguous spread (stage is strongest predictor of Multiple. night sweats.

PT aPTT normal normal normal normal normal normal normal prolonged normal prolonged normal prolonged prolonged prolonged prolonged normal or mildly prolonged normal normal prolonged normal prolonged prolonged normal normal prolonged prolonged prolonged prolonged prolonged prolonged normal normal normal normal normal prolonged normal decreased .

Anti-HBcAg-IgM Anti-HBcAg IgG + - . + . + . - .

decreased when due to decreased production platelet aggregation and other specialized studies Factor VIII assay Factor IX assay vWF assay fibrin and fibrinogen degredation products low levels of gpIIb/IIIa low levels of gp1b hereditary angioedema d/t deficiency of C1inhibitor gene .Confirmatory Tests or Other Significant Findings megakaryocytes normal or increased when thrombocytopenia is caused by increased platelet destruction.

Anti-HBsAG - - + + .

.

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children.EBV associated.because malaria decreases resistanc) • Sporadic.Disorder Classification Lymphoid Neoplasms Precursor B-Cell Neoplasms B-Cell Acute Lymphoblastic Leukemia/Lymphoma (B-ALL) Leukemia Precursor T-Cell Neoplasms T-cell acute lymphoblastic leukemia/lymphoma (T-All Leukemia Peripheral B-Cell Neoplasms • Lymphoma-divided into 3 main clinical variants: • Endemic(malarial regions.weel differentiated .MALToma Follicular lymphoma Lymphoma.non African where malaria is not holoendemic.less commonly jaw ileocecal is common Burkitt Lymphoma • Immunodeficiency associated lymphoma Diffuse large B-cell lymphoma Lymphoma Extranodal marginal zone lymphoma Lymphoma.

"knobby" type T-cell leukemia.histologically have in common presense of large pleomorphic cells Anaplastic large-cell lymphoma that express CD30 and T cell markers . Peripheral T-Cell lymphoma angioimmunoblastic non-hodgkin lymphoma: 4 clinical entities all sharing same name. anaplastic. T-prolymphocytic T-Cell prolymphocytic leukemia leukemia/t-cell lymphocytic leukemia Large granular lymphocytic leukemia Leukemia Mycosis fungoides/Sezary syndrome cutaneous T-Cell lymphoma Non Hodgkin Lymphoma.well differentiated leymphocytic Lymphocytic (SLL) lymphoma Peripheral T-Cell and NK cell Neoplasms T-Cell chronic lymphocytic leukemia. Cutaneous (mycosis/sezary).all T-cell lymphomas that are not contained in the 4: Extranodal.Hairy Cell leukemia Leukemia-TRAP Lymphoma.intermediate differentiated Mantle cell lymphoma lymphocytic lymphoma Chronic Lymphocytic Leukemia (CLL)/Small Leukemia.

with prominent proliferation of high endothelial venules and Angioimmunoblastic T Cell Lymphoma follicular dendritic cells Hodgkin Lymphoma Lymphoma Classical subtypes Lymphoma Lymphoma.cutaneous T-cell extranodal NK/T-cell lymphoma lymphoma.collagen bands that surround at leaset one nodule and Hodgkin Reed Sternberg Nodular sclerosis cells with lacunar morphology Mixed cellularity Lymphoma Lymphoma.Adult t-cell leukemia/lymphoma T-Cell Leukemia not in typical lymph node. subcutaneous t-cell lymphoma NK cell leukemia SEE large granuar lymphocytic leukemia peripheral T cell lymphoma characterized by systemic disease.classical HL with scattered Reed- sternberg cells and nodular or less commonly a diffuse cellular background of small lymphocytes. polymorphous infiltrate involving lymph nodes.absense of neutrophils and Lymphocyte rich eosinophils .

lymphocyte depletion Lymphoma Lymphocyte predominance Lymphoma malignant disease of plasma cells in bone marrow.monoclonal immunoglobulin in serum or urine without MGUS (Monoclonal Gammopathy of clinical features of multiple myeloma or undetermined sign) macroglobulinemia MYELOID NEOPLASMS . second most common hematological Multiple Myeloma cancer Plasmacytoma plasma cell neoplasm that forms a discrete mass small lymphocytic lymphoma with plasmacytic differentiation: cross between multiple myeloma Lymphoplasmacytic (Waldenstrom and small lympocytic lymphoma. immunocytoma plasma cell neoplasm.also called Macroglobulin) plasmacytoid lymphoma.

Leukemia: Subclassification by cytogenic
abnormalities, lineage, or surface markers-
Acute Myeloid Leukemia M3:promyeloblast(MPO+

leukemia: Classified into 3 phases based on
Chronic Myeloid Leukemia clinical characteristics and labaratory findings

Myelodysplastic Syndromes based on number of blasts in marrow
clonal neoplastic proliferations of myeloid stem
Myeloproliferative syndromes cells

Cell Type & Location Epidemiology

Children below 10, down syndrome
B cell precursor arising from bone children older than 5, most
marrow commonly children between 2-5

immature T cell proliferation from Children, lymphoma version is
thymus adolescent males

B cell arising from Germinal Center

B cell lymphoma arising from
marginal zone or Germinal center 70 year old median age

diverse group of B cell neoplasms
from lymph nodes, spleen,
extranodal tissue
B-Cell lymphoma arising from
Germinal Center

B cell leukemia arising from mature
B cells middle aged caucasion men

B cell lymphoma arising from
mantle zone- CD19,20,5+ CD23-

leukemia arising from naïve B cell in 75% of diagnosed patients are over
bone marrow 50

mature- post thymic T cell adults over 30- median 60

adults-rare, only 2-3k% of chronic
Cytotoxic T cells or NK cells lymphoprolif d/o

Helper T-Cell- CD4+ mature adults

10% non-hodgkin lymphomas-
Helper or Cytotoxic T cells mainly older adults

children and young adults-most
commonly men- increased risk with
T-Cell silicone breast implants

is uncommon) 20-25% of all CHL peripheral lymph nodes. 70% of all HL eosiniphils and plasma cells- eosinophils d/t IL-5 secretion- Cervical and supraclavicular lymph nodes. spleen or lung (bone. 15-34 5.more frequent in spleen.3. liver.30% of all nodes. males 43 yrs.2% respectively) years of age.single or chain of older than 50.spread contguously lymphomas. peripheral lymph nodes. mediastinum. bones.3% incidence in Asia for Cell is rare lymphoma ● 15-20% of peripheral T-cell lymphomas ● 1-2% of non-Hodgkin lymphomas mature CD$+ follicular T cell. males 38 years.some ● M:F ratio 1:1 involve sleepn. mediastinal. lungs. liver. ● More common in Caucasians than pleuopulmonary and bone marrow in Africans or Asians bimodal age group. 1% of all cancers cervical lymph nodes. bone marrow. and Caribbean Nkcell (most common) cytotoxic T adults.Mature CD4+ T-Cells that are Adults • Mainly in Japan. skin. marrow. bulky disease. bulky disease.at ● Middle aged and elderly patients lymph nodes primary site. liver (mediastinum HIV pts and developing countries. late 20s and lymph nodes. west infected africa.5% of all classical waldeyer's ring Hodgkin lymphoma . marrow and liver uncommon but similar males and females.

predilection for retroperitoneal lymph nodes. hematopoietic neoplasms 3-5% plasma cell neoplasms- isolated of bone or soft tissue (oropharynx) of terminally differentiated B cells. incidence Plasma cell increases with age (64 years) .peripheral lymph males. or primary lymph node ● Rare (2% of hematopoietic neoplasms) malignancy of older patients (50-69 years) with involvement of bone marrow. bone marrow. higher prevalence in African americans.<1% of all hodgin marrow involvement is common lymphoma. spleen and liver ● May affect nerve roots. extramedullary. lymph node. males.can be either solitary of bone.30-37yrs B cell origin. meninges and rarely brain or small intestine more common than multiple myeloma. uncommon-5%of Hidgkin nodes lymphoma neoplastic proliferation of plasma older individuals (increase risk 1-2% cells with multifocal skeletal each year) 10-15% of involvment. abdominal organs.90% have subdiaphragmatic disease or organomegaly.

myeloid-monocytic.from either a myeloid stem cell or a myeloblast: 5 classes based on predominant cell type: Myeloid. megakaryocytic onset from either a stem cell or a myeloid stem cell . 50yr erythroid. monocytic. incidence increases with age.

MYC and p21 lesion begins as reactive polyclonal reaction to autoimmune disorder or infectious disease (Sjogren. Hashimoto thyroiditis. 9. BCL6.Etiology • chromosomal translocations t12. MUM1.21 CBFα and ETV6 in 25%. Helicobacter gastritis) 14. HLA-B mutations • Immunohistochemical staining show BCL2. COA1. LMO2. PVT1.14 translocation! EBV.22(philadelphia as well) • Chromosomal translocations- NOTCH1 mutations 50%-70% 8.C-myc gene translocation on chromosome 8 and immunoglobulin heavy chain of chromosome 14 • EXOC2 gene.18 translocation (Bcl-2) .

an uncommen cancer .5 translocation most common.2.translocation fo 11. abnormalities of chromosome 8 postulated that T-LGL are transformed cytotoxic Ts with β chain rearrangements for T cell receptor and clonal rearrangement of γ chain receptor no known chromosomal abnormality no specific chromosomal abnormality cytotoxic cell rearrangement of ALK 2p23.14.bcl1-cyclin D and immunoglobulin heavy chains clonal rearrangements for γ and δ chains.inversion of chromosome 14.

HTLV1 provirus is present in cells EBV associated (B cells EBV+) but T cells are EBV negative. X most common subtype (65-70%) rare form composed of reactive lymphocytes. 5.clonal rearrangement of T-cell recempot genes or IgH.associated with EBV in 40% cases .chromosomal abnormalities 3.

megakaryocytes (GPIIbIIIa) erythroid cells (glycophorin) waldenstrom's macroglobulinemia is a clinical syndrome defined by serum IgM monoclonal gammopathy.express antigens associated with myelomonocytes(CD33).often HIV associated cell or origin is less differentiated thaan plasma cell. monoclonal Ig light chains in urine (bence jones) hyperviscocity syndrome and B cell neoplasm involving marrow- including lymphoplasmacytic lymphoma ? .

22 BCR fusing with ABL leading to constitutive activation of tyrosine kinase IL3betac receptor . 3. 1:12 translocation.17 translocation PML-RARα inhibits differentiation.21 Philadelphia chromosome 9.t15.

E2A or EBF genes • 12.21 translocations • loss of function generally leads to unchecked growth or disinhibition of apoptosis proliferation due to mutation in Notch1 which makes it constitutively active singling the cell to constantly proliferate associated with mucosal tissue disseminated disease in more advanced stage .Pathogenesis • constitutive activation of tyrosine kinase receptor causes unchecked proliferation of lymphoblastic cells (9-22 translocation) • loss of function mutations in PAX5.

diffuse not nodular lymph node proliferation. but no lymphadenopathy • Small lymphocytic lymphoma. plaque.proliferation of small B cells with B markers and 1 T marker (CD5) like B-chronic lymphocytic leukemia • B chronic lymphocytic leukemia: 95% of cases. CD20. peripheral findings show increased normal lymphocytes.unchecked proliferation leads to increasing damage in the DNA which causes other mutations and then cancer . B cell markers CD19. T cell markers. then tumor phase helper or cytotoxic t cells efface the lymph nodes by over proliferation and activation of eosinophils constitutively active tyrosine kinases trigger signaling pathways that cause unchecked proliferation. Cells must be CD23 positive but CD10 negative • T chronic lymphocytic leukemia: 5% of cases. T cell marker present CD5.splenomegaly (red pulp). smudge cells (from fragile neoplastic lymphocytes) Bone marrow with numerous neoplastic lymphocytes most common type of mature T-Cell leukemia CD4+ cells hone to skin producing 3 phases: premycotic(inflammatory).

hypercalcemia and lytic bone lesions (because of RANKL induction) destructive extranodal masses.HTLV1 provirus infects and causes circulating lymphocyte proliferation with an irregular nuclear contour.sinonasal most common (destructive nasopharyngeal) Testis and skin are less common.tumor invades small vessels causing extensive ischemic necrosis expansion of EBV+ B cells due to immunodeficiency lymph node has broad collagen bands. Reed sternberg cell variant present in nodular sclerosis is called Lacunar cell. leading to visceral involvement.clear space surrounding malignant tumor cell .

failing kidney) Extramedullary plasmacytoma: ● Arises outside bone marrow. lung or any other body site ● May recur locally.lead to renal failure in 20-30%. bone marrow) no lytic bone lesions. Anemia (shift myeloid to lymphoid progenitor cell. oropharynx. stimulate MIP1αand RankL to stimulate osteoclast (osteoclast stimulates everything with IL6) so increase calcium in blood leads to neuronal tetany. many reed-sternberg cells lympho-histocytic variants. serum calcium does not increase paraprotein discovered unexpectedly. spleen. 15% IgM. sinuses. 12%IgA.few lymphocytes. neoplastic cells infiltrate many organs (lymp nodes. 3% . but only infrequently progresses to myeloma. over produciton of plasma cells in marrow. often in nasal cavity. nasopharynx. and light chains get filtered thru glomerulus in kidneys. secrete DKK1 (inhibit OPG osteoblast). less often than solitary plasmacytomas of bone ● Morphologic features similar to solitary plasmacytoma of bone has an M spike.70% IgG.L&H cells.popcorn cells that are negative for CD15 and CD30 a whole bunch of light chains are produced and (IgG and IgA) and these plasma cells produce and secrete IL3 (inhibit osteoblast progenitor).when the light chains urinated they are called Bence Jones proteins.

nuclear budding. accumulates genetic changes that freeze the cell in immature state and prevent differentiation. "pawn ball" megakaryocytes bone marrow is markedly hypercellular. Other mutations disrupt genes controlled by differentiation leading to uncontrolled growth of immature clone cells constitutive activation speeds up cell division and inhibits dna repair causing genomic instability and makes cell more susceptible to further abnormalities dysplastic changes: Pelger Huet cells (aviator glasses nuclei) ring sideroblasts. all cell lines ar eincreased in number .myeloblast. normal precursor of white blood cells.

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bleeding • Bone pain and tenderness d/t marrow expansion • Generalized lymphadenopathy. stormy onset.days to weeks • Depressed marrow function symptoms: fatigue. splenomegaly. retroperitoneum. aggressive rapidly proliferating tumor . fever. hepatomegaly • CNS manifestations d/t meningeal spred General acute leukemia symptoms + mediastinal mass.Signs and Symptoms • Abrupt. ovaries) high incidence in AIDS high grade lage cell B-lymphoma with diffuse growth pattern.may compress SVC african type involves mandible or maxilla associated with EBV. american type nonendemic sporadic involves abdomen (bowel.

hepatomegaly. skin. generalized lymphadenopathy.high lymphocyte count with anemia and thrombocytopenia are common. neutropenia occurs even tho there is no marrow infiltration sezary variant because it is disseminated where skin manifests as generalized exfoliative erythroderma. plaques. hepatosplenomegaly. or anemia hepatosplenomegaly. hypogammaglobulinemia Indolent course initialy mild to moderate lymphocytosis and splenomegaly. spleen.000) without adenopathy.000) with or without lymphadenopathy. thrombocytopenia • Stage 1: absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly. or splenomegaly • Stage 4: absolute lymphocytosis and thrombocytopenia (<100. generalized erythema. pruritis. liver. enlarged spleen • Stage 0: absolute lymphocytosis (>15. marrow. splenomegaly. nodes.dry tap bone marrow aspiration. indolent generalized lymphadenopathy with eosinophilia. skin infiltrates cells can be found in peripheral blood. or thrombocytopenia • Stage 2: absolute lymphocytosis with either hepatomegaly or splenomegaly with or without lymphadenopathy • Stage 3: absolute lymphocytosis and anemia (hgb<11) with or without lymphadenopathy. wieight loss lymph node systemic involvement in 2. anemia. hepatomegaly. nodules. mycosis has cutaneous patches. indolent leukemia. and cutaneous soft tissue disease in the other . anemia.

or 1.• Adults with cutaneous lesions RASH • Marrow involvement • Hepatosplenomegaly • Generalized lymphadenopathy • Peripheral blood lymphocytosis • Hypercalcemia.B-cell symptoms (Pel Ebstein fever that comes and goes) weight loss. weight loss. pleural effusion.hepatosplenomegaly. more often stage III or IV B symptoms are rare. skin rash (pruritis). polyclonal hypergammaglobulinemia. ascitis painless enlargement of lymph nodes. night sweats most present with stage II.lytic bone lesions • Aggressive usually presents with advanced stage disease. fever. B symptoms in 40% B symptoms are frequent. arthritis. Stage 1 or 2 presentation .

similar to other extramedullary plasmacytomas hyperviscosity syndrome (because IgM is BIG) visual abnormalities d/t vascular dilations and hemorrhages in retina. infections. anemia. renal failure.more advanced stage and with B symptoms at presentation. mean 5 cm. lytic bone lesions(HRAL) Primary lymph node plasmacytoma: ● Rare. 3% biclonal. must exclude metastatic multiple myeloma (40% of high stage myelomas metastasize to lymph nodes). stage 1 or 2 presentation anemia. renal insufficiency. 40% had serum monoclonal proteins. fractures. metastatic upper respiratory tract plasmacytomas (15% metastasize to cervical lymph nodes) and Castleman’s disease ● Often involves cervical nodes. bleeding and cryoglobulinemia which precipitate at low temps and may cause raynaud phenomenon and cold urticaria Paraprotein is usually discovered unexpectedly: 70% IgG. bone lesions) . Neurologic headaches and confusion. monoclonal light chain in urine in 1/3 ● Serum immunoglobulin level less than 3g/dl ● No myeloma-related organ or tissue impairement (no CRAB features related to myeloma: hypercalcemia. more aggressive than other subtypes. may be part of continuum with mixed cellularity subtype indolent. 12% IgA. dehydration.nodular behavior in young ment with cervical or axillary adenopathy. proteinuria. 15% IgM. most patients had localized disease and were cured after local excision or radiation.

cytogenic evolution with new abnormalities in addition to Philadelphia chromosome. abdominal fullness • accelerated phase. joint or hip pain. left side pain. Large clusters of blasts in bone marrow on biopsy. chloroma development . thrombocytopenia.000 or more than 1 mil. symptoms happen early • chronic phase: asymptomatic or mild symptoms of fatigue. platelet count <100. neutropenia.10-19% myeloblasts in blood or bone marrow.related to replacement of normal bone marrow by leukemic cells- anemia. >20% basophils in blood/marrow. increasing splenomegaly • Blast crisis: >20% myeloblasts or lymphoblasts in blood or bone marrow.

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TdT positive biopsy of lymph node. Basophilic cytoplasm and larger nuclei. CSF cytology and PET- . abdomen and pelvis. Interspersed starry sky macrophages • Histochemical studies • differentiated from B cell by CD markers (generally T cell are below 10) • myeloperoxidase negative PAS positive. Nucleoli absent or inconspicuous. bone marrow biopsy. Nucleoli absent or inconspicuous. Interspersed starry sky macrophages • Histochemical studies • differentiated from T cell by markers (over 10) CD10. Nuclear chromatin is delicate and stippled. TdT positive • CBC and peripheral blood smear show blast cells • Bone Marrow Exam shows blast cells between 25-95%. staging includes CT of chest. 19.20 • myeloperoxidase negative PAS positive. Nuclear chromatin is delicate and stippled.Diagnosis acute lymphoblast are all TdT positive • CBC and peripheral blood smear show blast cells • Bone Marrow Exam shows blast cells between 25-95%. Basophilic cytoplasm and larger nuclei.

PAS positive T-lymphocytes are present in epidermis immunophenotyping: mature T-Cell phenotype: CD2. paranuclear eosinophilic region(doughnut cells) and abundant cytoplasm (may express CD3 or CD4) only 1 systemic type expesses ALK . then demonstrated wth abnormal B lymphocytes in blood.lymphocytes have hairlike cytoplasmic projections. αβ or γδ. receptors.cluster differentiation 5 and cd23 present HTLV-1 negative.5. serum gamma globs normal. TRAP stain diagnostic first suspected with lymphocytosis.3.hallmark cells and CD30+- recognition of large cells with pleomorphic kidney shaped nuclei.CD56+ for NK cell variants sezary cells on blood smear have cerebriform like nuclei. helper or cytotoxic origin (CD 4 or 8) examination of enlarged lymph node. no paraporteins present immunohistochemistry of cells reveals CD3+ T cell vriants or CD3-. express adhesion molecule CLA and chemokin CCR4 and CCR10 which hone to skin.

Cells with mutlilobed nuclei (clover leaf or flower cells). they have killer Iglike receptors.HTLV1 antibody is detected in serum.lytic bone lesions large azurophilic granules are seen in tumor cells that resemble NK cells. express CD3 and NK cell markers Cytology● Small to large cells with moderate to faint basophilic cytoplasm without azurophilic granules and sometimes with microvacuoles. moderately condensed chromatin . often irregular or indented nuclei.

CD108- ● <10% clonal plasma cells in bone marrow ● Plasma cells lack nucleoli . anemia. plasmacytosis no light chain restriction of plasma cells ● IgM monoclonal gammopathy of any concentration ● Bone marrow infiltration by small lymphocytes showing plasmacytoid or plasma cell differentiation ● Intertrabecular pattern of bone marrow infiltration ● Immunophenotype is surface IgM+. CD19+. lytic bone lesions) differential: myeloma cells are mor anaplastic.monoclonal plasma cells in bone marrow. presence of one or more of following (hypercalcemia. CD23-. CD27+. presence of monoclonal antibodies in serum or urine. CD20+. FMC7+. CD22+. >10%. CD103-. renal insufficiency. CD5 variable. CD25+. CD10-.

Bone marrow biopsy. punched out nucleus with an aur rodd Blasts in blood. basophils and eosinophils increased (differentiate from leukemoid reaction). CBC shows increased granulocytes.crystal aggregates of MPO(auer rods). cytogenetics detechs philadelphia chromosom .low cytoplas.

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PAX5. Neutropenia. Neutropenia. Ce20 scrotum and CSF needed Anemia.Labs Treatment Anemia.prophylaxis to CD10.2. Thrombocytopenia. Thrombocytopenia. Immunohistochemistry:preB cells are arrested at stages preceding surface immunoglobulin excellent response to expression so they express CD19. and chemotherapy.5&7 (CD2-8 NOT 10) starry sky benign macrophages-because they have engulfed macrophages of malignant lymphocytes chemotherapy with rituximab doesn't respond . ImmunohistochemistrypreT cells arrested at early intrathymic stages so often express CD1.

spleen. very indolent cancer medium sized lymphocytes with single nucleoli and basophilic cytoplasm with occasional blebs or projections. alemtuzumab lymphocytes helps but survival is still low Lymphocytosis. peripheral smear.smudge cells d/t delicate difficult to treat. bone marrow.but sarcomatoid. sites of involvment in peripheral blood. excellent response 2CDA which inhibits adenosine deaminase and increased levels of toxic deoxyadenosine (adenosine accumulates to toxic levels in neoplastic B cells(part of purine degredation pathway)) CBC. radiationchemotherapy. CHOP. signet ring good prognosis .irregular nuclear shape . liver aggregates are Pautrier microabscesses pleomorphic mixture of variably sized malignant T cells in lymph nodes blood smear morphologic variants: small cell (cells with same immunophenotype). treatment not needed in early immunohistochemistry stage.

hypercalcemia circulating immune complexes. cold agglutinins with hemolytic anemia. respond to steroids chemo and external beam radiotherapy survivors have increased risk for 2ndary nonhodgkin lymphoma or acute leukemia . anti-smooth muscle antibodies.may factor. positive rh moderately aggressive.

increased paraprotein.plasmapheresis for lymphocytes and lymphoplasmacytoid cells hyperviscosity and hemolysis ● Follow with serial measurements of monoclonal protein but usually no specific treatment . CT scan for lesions prognosis with cyclin D1+ with local radiatin smear: russel bodies (cytoplasmic immunoglobulin) & Dutcher bodies (intranuclear immunoglobulin) may be present● Moderate to severe normochromic anemia with marked rouleaux formation (like partially stacked coins) ● 30% have leukemia composed of no cure. decreased normal antibodies.Blood & Urine: (anemia. bone poor prognosis if no treatment. increased blood urea/nitrogen. abnormal RBC. 3 marrow biopsy >10% plasma cells. urinary bence jones) BONES: bone aspiration. increased creatinine.poorer osteoporosis. hypercalcemia. xray. years with chemotherapy.

peripheral blood in promyelocytic subtype with smear (blasts with auer rods) 15.altransretinoic acid immunohistochemistry. stem cell transplantation. CBC. Chemotherapy (induction and consolidation).17translocation targeted therapy by imatinib mesylate at BCR-ABL .

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22 has poor prognosis seen in adults (philadelphia chromosomes Ph+ALL) usually called acute lymphoblastic lymphoma most common type of non-hodgkin lymphoma.Complications/Other classic: 12. t9.21 has a good prognosis. subtypes immunodeficiency associated B- cell lymphoma(EBV).seen in kids. body cavity large B cell lymphoma(HHV8) .

3.Richter's syndrome (transformation of CLL to fast growing diffuse large B cell lymphoma).7. transformation to high grade lymphoma positive for pan-t antigens. warm autoimmune hemolytic anemia. hypogammaglobulinemia(infection). CD4+/CD8. negative for TdT and CD1a.CD2. CD4+CD8+ 25%. CD4-/CD8+ in 15% indolent tumors with long survival rate worse prognosis than mature comparable B cell neoplasms .in 60%.

rapidly progressive disease which is fatal in months to a year even with chemotherapy poor prognosis in advanced disease because they do not respond to chemotherapy. plasmacytoma.>90% for 5 years worse prognosis than nodular sclerosis but better than lymphocyte depleted . classical hodgkin lymphoma.mean survival <3 years. small b-cell lymphoma. peripheral t-cell lymphoma. but the do respond to radiation may progress to diffuse large B-Cell lymphom (common).death d/t infection worse prognosis depends on more reed-sternberg cells being present great survival.poor prognosis.

only 3% per year for the next 5 years and 1% per year for the subsequent 10 years ● Non-secretory myeloma: 3% of plasma cell myelomas show absence of M-protein by electrophoresis or immunofixation. peripheral blood cytopenias high beta2 microglobulin levels Risk of progression to overt myeloma is 1% per year.● Asymptomatic (smoldering) myeloma: patients with no related organ or tissue impairement. can evolve to myeloma. aggressive disease may have poorer prognosis than other small B cell lymphomas if advanced age. amyloidosis. Waldenstrom’s macroglobulinemia or other lymphoproliferative disorder . clinical features similar to secretory myeloma except for low incidence of renal insufficiency and hypercalcemia ● Plasma cell leukemia: clonal plasma cells > 20% of the leucocyte differential count. 10% per year progress to symptomatic myeloma for the first 5 years.

AML Subtype: Acute Promyelocytic Leukemia t(15.17) disrupts retinoic acid receptor so can't mature.promyelocytes. lots of auer rods which increases coagulation risk so DIC- treat with alltrans retinoic acid (ATRA) which causes them to go to neutrophils prognosis really good after imatinib are considred preleukemias because pt have an increased risk of developing acute leukemia .

Microscopy .

epithelioid histiocytes.● Bone Marrow: focal or diffuse involvement by small B cells with plasmacytic differentiation and cytoplasmic (Russell) and nuclear (Dutcher) PAS positive inclusions ● Inclusions are cytoplasmic immunoglobulin and are nonspecific ● Diffuse involvement is associated with decrease in normal hematopoietic cells ● Often has reactive mast cells. mature plasma cells .

associated with down syndrom before age of 5. • conditions that lead to AML.blast build up in bone marrow • myelodysplasia can also lead to AML because of low blood blood cell count if the blast builds up to over 20% • tissue form is called granulocytic sarcoma (chloroma) . infiltrates gums • megakaryoblastic leukemai.acute monocytic leukemia.myeloblasts build up without myeloperoxidase.myelodysplastic syndrome.often no myeloperoxidase.• monoblast AML.

DIC d/t release of thromboplastic substances in granules (especially when treatment kills tumor cells) 15.17 translocaation (PML and RARα) • M4.associated with acute myelofibrosis d/t release of platelet derived growth factor .• M0 undiferentiated myelogenous leukemia • M1 myeloblastic leukemia without maturation • M2 myeloblastic leukemia with maturation (some promyelocytes • M3.myelomonocytic leukemia with both myeloblasts and monoblasts • M5 monocytic leukemia (gingival infiltrates) • M6 erythroleukemia (Di Guglielmo disease) abnormal erythroid precursor that show binucleate and megaloblastic changes • M7 acute megakaryocytic leukemia.hypergranular (microgranular) promyelocytic leukemia.Auer rods present.

Acute ia em uk Le Chronic Hodgkins as om ph m Ly B-Cell Non- Hodgkin's T-Cell Plasma Cell Neoplasms Malignant Benign Syndromes Leukemia= neoplasms with widespread involvment of bone marrow masses arising from lymph nodes.presentations often blur definitions .

acute lymphoblastic leukemia (ALL) Acute Myelogenous Leukemia (AML) Chronic lymphoblastic Leukemia (CLL/SLL) Chronic Myelogenous Leukemia (CML) Hairy Cell Leukemia Lymphocyte Predominant (LP) type Lymphocyte Depleted (LD) Type) Lymphocyte Rich (LR) type Mixxed Cellularity type Nodular Sclerosis Small Lymphocytic Lymphoma (CLL/SLL) Follicular Lymphoma Diffuse Large B-Cell Lymphoma Burkitt's Lymphoma Lymphoma) MALToma (marginal zone lymphoma) Lymphoplasmacytic lymphoma (Waldenstrom) Lymphoblastic Lymphoma Peripheral T-Cell Lymphoma Micosis Fungoides (MF)& Sezary Syndrome (SS) Adult T-Cell Leukeumia-Lymphoma Anaplastic Large Cell Lymphoma Multiple Myeloma Plasmacytoma Lymphoplasmacytic (Waldenstrom Macroglobulin) MGUS (Monoclonal Gammopathy of undetermined sign) Chronic Myelogenous Leukemia (CML) Polycythemia Vera Essential Thrombocythemia Myelofibrosis .

Pathophysiology Etiology & Age Group type chronic lymphocytic leukemia T-ALL proliferation and non differentiation of immature T-Cell.goes to thymus. forms lymphoma teenage boys .

Clinical Manifestations Diagnosis Treatment

Disorder
Leukopenia

Leukopenia

Neutropenia
Eosinopenia
Lymphocytopenia
Leukocytosis
eosinphilia

neutrophilia
Lymphocytosis
basophilia

Lymphadenitis

Acute Nonspecific Lymphadenitis
Chronic Nonspecific Lymphadenitis

Classification

Neutropenia, Agranulocytosis

suppurative lymphadenitis

Typical Patient .

cat scratch disease. tularemia. lymphogranuloma venereum. bubonic plague. kikuchi disease. mesetneric lymphadenitis.Necrosis: anthrax. IV drug use.. immune destruction (SLE) septic shock infection (acute appendicitis). Staphylococcal infection. meliodosis. typhoid fever . sterile inflammation with necrosis (acute MI) drugs (corticosteroids) most commonly S.aplastic anemia o Infiltrative marrow disorders o Suppression ofo commited precursors o Disease states by ineffective granulopoiesis o Inherited conditions (Kostmann syndrome. ipairing differentiation) • Accelerated removal or destruction of neutrophils o Neutrophil injury by immunologic disorders (SLE) or drug exposures o Splenic sequestration o Increased peripheral utilization in overwhelming infections aplastic anemia. aureus infection.Cause o BSC suppression.

early phase dilated sinus contain proteinaceous fluid with granulocytes and macrophages that infiltate parenchyma and create microabscesses.Pathogenesis decreased production. catecholamines. increased destruction (complement/macrophages).LATE phase lymphocytes plasma cells macrophages and debris are inside lymph node . lithium regional lymph nodes infected by draining from pyogenic site- superficial nodes most common. activation of neutrophil adhesion molecules (increase number of neutrophils adhering to endothelium by endotoxins) increased bone marrow production of neutrophils or decreased activatio of adhesion molecules d/t corticosteroids.bacteria may be present.

buccal mucosa. pharynx • Opportunistic infections • Infections fulminant • Broad spectrum antibiotics at first sign infection! Fever .Signs and Symptoms • Interrcurrent infections • Malaise • Chills • Fever • Marked weakness and fatigability • Ulecerating necrotizing lesions of gingiva.

Diagnosis WBC<1500 .

Labs .

Treatment .

Complications/Other .